Over the past few years, a number of laboratories have become involved in determining the feasibility of utilizing the molecular techniques of gene manipulation or gene therapy as part of the strategy for the treatment of human immunodeficiency virus (HIV) infection. One approach has been to transduce into peripheral blood CD4+ T cells selected genes of HIV which have been mutated and which can serve as trans-dominant mutants to block the expression of HIV if that cell ultimately became infected. Ideally, stem cells might be transduced and reinfused into the host thus providing a progeny of cells which are resistant to HIV infection and or expression. Another approach to gene therapy has been to transduce into peripheral blood cells genes for substances that when secreted or expressed would protect the cells themselves or surrounding cells from HIV infection. In this regard, we have successfully transduced, using retroviral vectors, cell lines and peripheral blood lymphocytes with a gene that expresses soluble CD4-IgG and have partially protected these cells against spreading HIV-1 infection.